14 human health risk assessment Flashcards
what is risk?
what is the table of chemicals and their problems?
what are the two types of risk assessment?
prospective risk assessment
-future
-ex: pharmaceutical, during same process as registration
retrospective risk assessment
-in the past
-ex: pesticides, because only really analyze risk after its approved
risk assessment: to decribe the overall process or method where you:
-identify hazards and risk factors that have the potential to cause harm (hazard identification)
-analyze and evaluate the risk associated with that hazard (risk analysis, and risk evaluation)
-determine appropriate ways to eliminate the hazard, or control the risk when the hazard cannot be eliminated (risk control)
why is risk assessment important?
-create awareness of hazards and risk
-identify who may be at risk (populations and subpopulations at risk)
-determine whether a control program is required for a particular hazard (more in terms of environmental impacts, like dont flush drugs down the toilet)
-determine if existing control measures are adequate or if more should be done
-prevent injuries or illnesses
-prioritize hazards and control measures
what are the four elements of risk assessment?
what is hazard identification?
-inherent potency of chemical to cause harm to humans, animals and/or the environment
-does a chemicals of concern cause and adverse effect? (epidemiology, animal studies, short term assays, structure/activity relationships
evaluation of data on:
-harm to humans (health hazards, also birth defects, cancer, etc)
-harm to the environment
classification and labelling
-hazard and precautionary statement under the globally harmonized system (GHS)
-hazard symbols
are there available epidemiological or clinical data? (hazard identification)
what types of studies were used (e.g. ecologic, case control, cohort)?
-cross-sectional study: sampling a population at a given point in time to assess prevalence of a disease
-case-control: compares previous exposure in subjects with disease with one or more groups of subjects without disease
-cohort: population of subjects with disease with one or more groups of subjects without disease
-clinical trials: the investigator controls treatment (exposure)
what is the second element of risk assessment?
exposure assessment
what is the overview of exposure assessment?
what exposures are experience or anticipated under different conditions?
-identification of exposed populations
-identification of routs of exposure
-estimation of degree of exposure
what are the key components of exposure assessment?
-what are the most significant sources of the exposures?
-what populations were assessed?
-what are the key descriptors of risk?
-is there reason to be concerned about cumulative or multiple exposures?
-what are the conclusions of the exposure assessment?
is there reason to be concerned about cumulative or multiple exposures? (exposure assessment)
-ethnic, racial, or socioeconomic reasons?
what is the third element of risk assessment?
effect assessment
-critical element of hazard characterization
-as the dosage of a toxicant is increased, the toxic response (in terms of severity and/or incidence of effect) also increases
-to define a threshold of exposure above which the test substance will cause adverse effects
how is the identified adverse effect influenced by the level of exposure? (effect assessment)
-quantitative toxicity information collected
-dose-response relationships established
-extrapolation of animal data to humans
what are some difficulties for the quantitative toxicity? (effect assessment)
-one must decide on the critical endpoint to measure as the “response”
-one must also decide on the correct measure of “dose”
-interspecies extrapolation aspects: appropriate units for dose, administered dose versus absorbed dose versus target organ dose
what is the selection of critical data of effect assessment?
available human data are usually insufficient for this purpose
using animal data:
-exposure to the toxicant has been carefully controlled
-concurrent exposures to other toxicants have been minimized
what to do once all the data from several animal studies are reviewed? (selection of critical data)
-identify the animal model that is most relevant to humans (using comparative pharmacokinetic data)
-in the absence of a clearly most relevant species, the most sensitive species will be selected
-always assume that humans are as sensitive as the most sensitive species tested
what data were used to develop the dose-response curve? (effect assessment)
animal data:
-which species were used?
-were the data based on the most sensitive species, average of all species, or other?
-were any studies excluded and why?
epidemiological data:
-which studies were used?
-were only positive studies used, all studies or other combination?
-were any studies excluded and why?
what model was used to develop the dose-response curve? (effect assessment)
-what rationale supports this choice? is chemical-specific information available to support this approach?
for noncarcinogenic hazards:
-how was acceptable range calculated?
-what assumptions and uncertainty factors were used?
-what is the confidence in the estimates?
for carcinogenic hazards:
-what dose-response model was used?
-data about possible mechanisms of action?
-what is the basis for selection of the particular dose-response model used?
what is equation used in effect assessment?
-in an experimental exposure level study, the highest level tested in which “no adverse effect” was demonstrated is called “no observed adverse effect level” (NOAEL)
-the reference dose (RfD) is derived from the NOAEL by consistent application of uncertainty factors (UFs) and modifying factor (MF)
RfD=NOAEL/(UFs x MF)
what are UFs?
uncertainty factors: generally multiples of 10
-10-fold: when extrapolating from valid results of long-term studies on experimental animals when results of studies of human exposure are not available or are inadequate
-10-fold: when extrapolating from less than chronic results on experimental animals when there are no useful long-term human data
-10-fold: when deriving an RfD from a LOAEL, instead of a NOAEL. This factor is intended to account for the uncertainty involved in extrapolating from LOAELs to NOAELs
LOAEL=lowest observed adverse effect level
what is MF?
modifying factor
-use professional judgment to determine the MF, which is an additional uncertainty factor that is greater than zero and less than or equal to 10
-the magnitude of the MF depends upon the professional assessment of scientific uncertainties of the study and data base not explicitly treated in Ufs
-the default value is normally 1
what is the dose vs effect graph?
how is RfD useful?
-the RfD is useful as a reference point from which to estimate the potential effects of the substance at other doses
-doses less than the RfD are not likely to be associated with adverse health risks (less likely to be of regulatory concern)
-exposures exceeding the RfD increase, the probability of adverse effects in a human population increases
what is the last element of risk assessment?
risk characterization
-what is the estimated likelihood of the adverse effect occurring in a given population?
-estimation of the potential for adverse health effect to occur (quantitative estimates)
-evaluation of uncertainty
-risk information summarized and use in the risk management process
what are quantitative estimates of risk?
-to determine the likelihood of an adverse effect in an exposed population, quantitative information on exposure
-this process is different for carcinogens and for noncarcinogens
what the quantitative estimates of risk of noncarcinogens?
-involves a comparison between the predicted total exposures from all relevant exposure pathways and the exposure limits for each chemical of concern
hazard quotient (HQ)=MDD/RfD
-MDD=maximum daily dose from exposure assessment
-RfD=reference dose (or ADI=acceptable daily intake)
What does HQ mean in noncarcinogens?
-according to health canada, exposures associated with a HQ less than or equal to 0.2 is negligible
-HQ value would be less than or equal to 1.0->no adverse health effects would be expected
-HQ is greater than 1.0 and less than 10, it may indicate some potential risk, but the significant of this risk must be re-evaluated (assumptions made during the risk assessment)
-if the HQ is greater than 10.0, this indicates that there is an increased likelihood of potential health risks-> risk management measures
what are quantitative estimates of risk of carcinogens?
-for carcinogenic substances, the risk estimate, i.e. estimation of lifetime risk for carcinogens is determined by the following equation:
Risk=LADD x SF
-LADD= lifetime average daily dose (mg/kg/day)
-SF= cancer slope factor/cancer potency factor (mg/kg/day)^-1
what does risk mean in estimates of carcinogens?
what is the description of uncertainty?
-analysis of the uncertainty associated with a health risk estimate involves each step of the risk-assessment process
-uncertainty analysis can take place at the time of each step of health risk assessment, but because it affects the eventual risk estimate, it is considered part of the final step of risk assessment-risk characterization
where does uncertainty arise?
-observational studies
-extrapolation from studies in animals to humans
-extrapolation from high to low dose exposures
-interindividual variability
in risk characterization, what are the possible judgment outcomes?
-unacceptable exposures
-uncertain exposures
-acceptable exposures
what are unacceptable exposures?
-implement health hazard controls
-the implementation of mitigation measures
-multiple exposures: higher exposures to higher toxicity agents should be controlled first
what are uncertain exposures?
-collect additional information
-further risk characterization or additional information gathering are recommended for exposures that not well understood, or for which acceptability judgments cannot be made with high confidence
what are acceptable exposures?
-establish a monitoring program
-may have to collect additional information (e.g. monitoring, toxicological, or epidemiological data)
-ensure that the risk mitigation measures are performing as expected
